Alpha-mercaptoketone based histone deacetylase inhibitors.
In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo.
Wash
Paul L
PL
Department of Chemistry, Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA.
Hoffman
Timothy Z
TZ
Wiley
Brandon M
BM
Bonnefous
Céline
C
Smith
Nicholas D
ND
Sertic
Michael S
MS
Lawrence
Charles M
CM
Symons
Kent T
KT
Nguyen
Phan-Manh
PM
Lustig
Kevin D
KD
Guo
Xin
X
Annable
Tami
T
Noble
Stewart A
SA
Hager
Jeffrey H
JH
Hassig
Christian A
CA
Malecha
James W
JW
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002614:Chelating Agents / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy; D011355:Prodrugs / Q000737:chemistry; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry
D000970:Antineoplastic Agents; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007659:Ketones; D011355:Prodrugs; D015032:Zinc